Currently there is scientific and public concern about whether exposure to contemporary ambient levels of so-called endocrine disruptors, such as polychlorinated biphenyls and p,p'-DDE, a metabolite of DDT, alter semen quality. This concern stems from studies showing that PCBs and p,p'-DDE are found in a large proportion of the general population, as well as limited studies suggesting possible associations of exposure to PCBs and p,p-DDE with semen abnormalities. The area of human health effects of endocrine disrupting chemicals was identified as a current topic for special emphasis by The National Advisory Environmental Health Sciences Council and staff of the NIEHS. They specifically identified expansion of this priority area into health effects in men including changes in fertility. We propose an epidemiologic study to determine whether PCBs and p,p'-DDE are associated with altered semen quality in a population exposed to contemporary ambient levels without specific exposure (i.e. occupational) to PCBs or p,p'-DDE. Detecting even an association of small magnitude may have large population effects because of the widespread distribution of PCBs and p,p'-DDE in the general population. A recently funded pilot project (R03) demonstrated the feasibility of the proposed hypothesis-driven study. The NIEHS funded pilot project confirmed our ability to successfully recruit study subjects, the sensitivity of serum PCB and p,p-DDE measurements, and that there is sufficient variability in the distribution of serum PCB and p,p'-DDE concentrations in the study population. The proposed hypothesis-based study is specifically designed to investigate the relationship between serum concentrations of PCBs and p,p'-DDE and semen parameters, which include: sperm concentration, motility, and morphology, as well as prevalence of spermatozoa DNA fragmentation. In addition, the relationship between serum PCBs and p,p'-DDE and reproductive hormones, including testosterone, free testosterone, sex hormone binding globulin, luteinizing hormone, follicle stimulating hormone and inhibin-B, will be investigated. Potential confounders, such as age, sexual abstinence time before semen sample collection, lifestyle factors (i.e. cigarette smoking), and metals (i.e. lead) will be measured and adjusted for in the analysis.